Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity

2018 ◽  
Vol 10 (426) ◽  
pp. eaag1328 ◽  
Author(s):  
Andrew W. Kraft ◽  
Adam Q. Bauer ◽  
Joseph P. Culver ◽  
Jin-Moo Lee
Keyword(s):  
Ischemic Stroke ◽  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Sensory Deprivation ◽  
Sensory Loss ◽  
Behavioral Recovery ◽  
Functional Reorganization ◽  
Sensorimotor Recovery

Recovery after stroke, a major cause of adult disability, is often unpredictable and incomplete. Behavioral recovery is associated with functional reorganization (remapping) in perilesional regions, suggesting that promoting this process might be an effective strategy to enhance recovery. However, the molecular mechanisms underlying remapping after brain injury and the consequences of its modulation are poorly understood. Focal sensory loss or deprivation has been shown to induce remapping in the corresponding brain areas through activity-regulated cytoskeleton-associated protein (Arc)–mediated synaptic plasticity. We show that targeted sensory deprivation via whisker trimming in mice after induction of ischemic stroke in the somatosensory cortex representing forepaw accelerates remapping into the whisker barrel cortex and improves sensorimotor recovery. These improvements persisted even after focal sensory deprivation ended (whiskers allowed to regrow). Mice deficient in Arc, a gene critical for activity-dependent synaptic plasticity, failed to remap or recover sensorimotor function. These results indicate that post-stroke remapping occurs through Arc-mediated synaptic plasticity and is required for behavioral recovery. Furthermore, our findings suggest that enhancing perilesional cortical plasticity via focal sensory deprivation improves recovery after ischemic stroke in mice.

scholarly journals CREB Regulates Experience-Dependent Spine Formation and Enlargement in Mouse Barrel Cortex

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Annabella Pignataro ◽  
Antonella Borreca ◽  
Martine Ammassari-Teule ◽  
Silvia Middei
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Brain Connectivity ◽  
Sensory Deprivation ◽  
Brain Regions ◽  
Camp Response Element Binding ◽  
Synaptic Circuits ◽  
Layer V

Experience modifies synaptic connectivity through processes that involve dendritic spine rearrangements in neuronal circuits. Although cAMP response element binding protein (CREB) has a key function in spines changes, its role in activity-dependent rearrangements in brain regions of rodents interacting with the surrounding environment has received little attention so far. Here we studied the effects of vibrissae trimming, a widely used model of sensory deprivation-induced cortical plasticity, on processes associated with dendritic spine rearrangements in the barrel cortex of a transgenic mouse model of CREB downregulation (mCREB mice). We found that sensory deprivation through prolonged whisker trimming leads to an increased number of thin spines in the layer V of related barrel cortex (Contra) in wild type but not mCREB mice. In the barrel field controlling spared whiskers (Ipsi), the same trimming protocol results in a CREB-dependent enlargement of dendritic spines. Last, we demonstrated that CREB regulates structural rearrangements of synapses that associate with dynamic changes of dendritic spines. Our findings suggest that CREB plays a key role in dendritic spine dynamics and synaptic circuits rearrangements that account for new brain connectivity in response to changes in the environment.

scholarly journals Experience-dependent plasticity mechanisms for neural rehabilitation in somatosensory cortex

2008 ◽  
Vol 364 (1515) ◽  
pp. 369-381 ◽  
Author(s):  
Kevin Fox
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Somatosensory Cortex ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Sensory Experience ◽  
Functional Rehabilitation ◽  
Central Nervous System Damage ◽  
Dependent Plasticity

Functional rehabilitation of the cortex following peripheral or central nervous system damage is likely to be improved by a combination of behavioural training and natural or therapeutically enhanced synaptic plasticity mechanisms. Experience-dependent plasticity studies in the somatosensory cortex have begun to reveal those synaptic plasticity mechanisms that are driven by sensory experience and might therefore be active during behavioural training. In this review the anatomical pathways, synaptic plasticity mechanisms and structural plasticity substrates involved in cortical plasticity are explored, focusing on work in the somatosensory cortex and the barrel cortex in particular.

scholarly journals Whisker row deprivation affects the flow of sensory information through rat barrel cortex

2017 ◽  
Vol 117 (1) ◽  
pp. 4-17 ◽  
Author(s):  
Vincent Jacob ◽  
Akinori Mitani ◽  
Taro Toyoizumi ◽  
Kevin Fox
Keyword(s):  
Spontaneous Activity ◽  
Information Content ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Neuronal Response ◽  
Sensory Deprivation ◽  
Sensory Information ◽  
Short Latency ◽  
Characteristic Analysis

Whisker trimming causes substantial reorganization of neuronal response properties in barrel cortex. However, little is known about experience-dependent rerouting of sensory processing following sensory deprivation. To address this, we performed in vivo intracellular recordings from layers 2/3 (L2/3), layer 4 (L4), layer 5 regular-spiking (L5RS), and L5 intrinsically bursting (L5IB) neurons and measured their multiwhisker receptive field at the level of spiking activity, membrane potential, and synaptic conductance before and after sensory deprivation. We used Chernoff information to quantify the “sensory information” contained in the firing patterns of cells in response to spared and deprived whisker stimulation. In the control condition, information for flanking-row and same-row whiskers decreased in the order L4, L2/3, L5IB, L5RS. However, after whisker-row deprivation, spared flanking-row whisker information was reordered to L4, L5RS, L5IB, L2/3. Sensory information from the trimmed whiskers was reduced and delayed in L2/3 and L5IB neurons, whereas sensory information from spared whiskers was increased and advanced in L4 and L5RS neurons. Sensory information from spared whiskers was increased in L5IB neurons without a latency change. L5RS cells exhibited the largest changes in sensory information content through an atypical plasticity combining a significant decrease in spontaneous activity and an increase in a short-latency excitatory conductance. NEW & NOTEWORTHY Sensory cortical plasticity is usually quantified by changes in evoked firing rate. In this study we quantified plasticity by changes in sensory detection performance using Chernoff information and receiver operating characteristic analysis. We found that whisker deprivation causes a change in information flow within the cortical layers and that layer 5 regular-spiking cells, despite showing only a small potentiation of short-latency input, show the greatest increase in information content for the spared input partly by decreasing their spontaneous activity.

scholarly journals Npas4 Expression in Two Experimental Models of the Barrel Cortex Plasticity

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Aleksandra Kaliszewska ◽  
Malgorzata Kossut
Keyword(s):  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Laser Microdissection ◽  
Aversive Stimulus ◽  
Brain Plasticity ◽  
Sensory Deprivation ◽  
Experimental Models ◽  
Early Gene ◽  
Cortical Circuits ◽  
Stimulation Of

Npas4 has recently been identified as an important factor in brain plasticity, particularly in mechanisms of inhibitory control. Little is known about Npas4 expression in terms of cortical plasticity. In the present study expressions of Npas4 and the archetypal immediate early gene (IEG) c-Fos were investigated in the barrel cortex of mice after sensory deprivation (sparing one row of whiskers for 7 days) or sensory conditioning (pairing stimulation of one row of whiskers with aversive stimulus). Laser microdissection of individual barrel rows allowed for analysis of IEGs expression precisely in deprived and nondeprived barrels (in deprivation study) or stimulated and nonstimulated barrels (in conditioning study). Cortex activation by sensory conditioning was found to upregulate the expression of both Npas4 and c-Fos. Reorganization of cortical circuits triggered by removal of selected rows of whiskers strongly affected c-Fos but not Npas4 expression. We hypothesize that increased inhibitory synaptogenesis observed previously after conditioning may be mediated by Npas4 expression.

scholarly journals Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

2020 ◽  
Author(s):  
Nora Jamann ◽  
Dominik Dannehl ◽  
Robin Wagener ◽  
Corinna Corcelli ◽  
Christian Schultz ◽  
...  
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Sensory Deprivation ◽  
Axon Initial Segment ◽  
Electrophysiological Recordings ◽  
Network States

SummaryThe axon initial segment (AIS) is an important axonal microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent cortical plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using an in vivo model of the mouse whisker-to-barrel pathway in combination with immunofluorescence, confocal analysis and patch-clamp electrophysiological recordings, we observed bidirectional AIS plasticity. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.

scholarly journals Cellular diversity of the somatosensory cortical map plasticity

2017 ◽  
Author(s):  
Koen Kole ◽  
Wim Scheenen ◽  
Paul Tiesinga ◽  
Tansu Celikel
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Meta Analysis ◽  
Explanatory Power ◽  
Sensory Maps ◽  
Neuronal Precursors ◽  
Cortical Map

AbstractSensory maps are representations of the sensory epithelia in the brain. Despite the intuitive explanatory power behind sensory maps as being neuronal precursors to sensory perception, and sensory cortical plasticity as a neural correlate of perceptual learning, molecular mechanisms that regulate map plasticity are not well understood. Here we perform a meta-analysis of transcriptional and translational changes during altered whisker use to nominate the major molecular correlates of experience-dependent map plasticity in the barrel cortex. We argue that brain plasticity is a systems level response, involving all cell classes, from neuron and glia to non-neuronal cells including endothelia. Using molecular pathway analysis, we further propose a gene regulatory network that could couple activity dependent changes in neurons to adaptive changes in neurovasculature, and finally we show that transcriptional regulations observed in major brain disorders target genes that are modulated by altered sensory experience. Thus, understanding the molecular mechanisms of experience-dependent plasticity of sensory maps might help to unravel the cellular events that shape brain plasticity in health and disease.

scholarly journals Sensory Loss and Delirium Among Medicare Beneficiaries

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 797-797
Author(s):  
Emmanuel Garcia Morales ◽  
Nicholas Reed
Keyword(s):  
Claims Data ◽  
Sensory Deprivation ◽  
Vision Impairment ◽  
Sensory Loss ◽  
Future Research ◽  
Sensory Impairment ◽  
Medicare Beneficiaries ◽  
Increase Risk ◽  
The Impact ◽  
Dual Sensory Impairment

Abstract Sensory impairment is prevalent among older adults and may increase risk for delirium via mechanisms including sensory deprivation and poor communication which may result in confusion and agitation. In the Medicare Current Beneficiary Study (MCBS), delirium was measured using a validated algorithm of claims data. Sensory impairment was defined as any self-reported trouble hearing or seeing, with the use of aids, and was categorized as no impairment, hearing impairment only (HI), vision impairment only (VI), and dual sensory impairment (DSI). Among, 3,240 hospitalized participants in 2016-2017, 346 (10.7%) experienced delirium. In a model adjusted for socio-demographic and health characteristics, those with HI only, VI only, and DSI had 0.84 (95% CI: 0.6-1.3), 1.1 (95% CI 0.7-1.7), and 1.5 (95% CI 1.0-2.1) times the odds of experiencing delirium compared to those without sensory impairment. Future research should focus on mechanisms underlying association and determine the impact of treatment of sensory loss.

Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics

2021 ◽  
pp. 107848
Author(s):  
Amir Ajoolabady ◽  
Shuyi Wang ◽  
Guido Kroemer ◽  
Josef M. Penninger ◽  
Vladimir N. Uversky ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Clinical Therapeutics

scholarly journals Altered Short-Term Synaptic Plasticity in Mice Lacking the Metabotropic Glutamate Receptor mGlu7

2002 ◽  
Vol 2 ◽  
pp. 730-737 ◽  
Author(s):  
Trevor J. Bushell ◽  
Gilles Sansig ◽  
Valerie J. Collett ◽  
Herman van der Putten ◽  
Graham L. Collingridge
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Short Term ◽  
Metabotropic Glutamate ◽  
Term Potentiation ◽  
Commissural Pathway ◽  
Frequency Facilitation

Eight subtypes of metabotropic glutamate (mGlu) receptors have been identified of which two, mGlu5 and mGlu7, are highly expressed at synapses made between CA3 and CA1 pyramidal neurons in the hippocampus. This input, the Schaffer collateral-commissural pathway, displays robust long-term potentiation (LTP), a process believed to utilise molecular mechanisms that are key processes involved in the synaptic basis of learning and memory. To investigate the possible function in LTP of mGlu7 receptors, a subtype for which no specific antagonists exist, we generated a mouse lacking this receptor, by homologous recombination. We found that LTP could be induced in mGlu7-/- mice and that once the potentiation had reached a stable level there was no difference in the magnitude of LTP between mGlu7-/- mice and their littermate controls. However, the initial decremental phase of LTP, known as short-term potentiation (STP), was greatly attenuated in the mGlu7-/- mouse. In addition, there was less frequency facilitation during, and less post-tetanic potentiation following, a high frequency train in the mGlu7-/- mouse. These results show that the absence of mGlu7 receptors results in alterations in short-term synaptic plasticity in the hippocampus.

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